The candidate is in his sixth year of postdoctoral (MD) study. He has completed an internal medicine residency at the University of Iowa, and will finish his pulmonary fellowship at University of Iowa this year. He has had a long term interest in environmental health problems evidenced by his work in preventative and environmental health in medical school. The first year of fellowship was an intensive clinical year. In the subsequent years he has spent >75% of his time in research. During this period, his interest in environmental lung disease lead him to develop an in vitro model of silica mediated epithelial injury. In addition, as an active investigator with Dr. Hunninghake's Occupational and Immunologic Lung Disease SCOR study, he was involved in studying the role of bronchoalveolar lavage in occupational, immunologic and idiopathic lung diseases. He is very strongly committed to a career in academic medicine and biomedical research. The purpose of this research is to gain an understanding of the cellular level of how silica injures the lung and how that injury can be prevented. The epithelium plays a critical role in maintaining homeostasis in the lung. An enlarging body of data shows that epithelial injury is an significant part of the pathogenesis of silicosis. Importantly, silica exposure disrupts the barrier function of the epithelium which has a viral role in maintaining the integrity of the alveolarcapillary barrier. In vivo, silica exposure also perturbs the pulmonary surfactant system, causing increased production and decreased catabolism. Little is known about the direct interactions of silica with the epithelium. Primary cultures of rat type II alveolar epithelial cells will be used for in vitro studies designed to determine how silica increases permeability and alters surfactant metabolism. The emphasis will be on understanding the cellular mechanisms of the silica actions. It is hoped that an understanding of the mechanisms will lead to ways to prevent or treat silicosis. Pulmonary surfactant can block some of the toxic effects of silica in vitro. The protective mechanism of aluminum will be pursued using the type II cell model, and the role of surfactant as a natural defense will be investigated with an in vivo rat model. The pulmonary division at the University of Iowa is an outstanding environment for performing biomedical research and developing the skills required for becoming an independent investigator. The internal medicine department and pulmonary division are very committed to biomedical research and provide junior researchers the necessary and protected time needed to succeed. The breadth of the department and the close ties to the University mean that ample expertise, equipment, and instructional programs are close at hand. Perhaps most important is the opportunity to work with Dr. Hunninghake's supervision. He is a highly regarded investigator who has been very successful at training individuals who continue to pursue careers in academic medicine and basic research. His lab is also experienced in, and well equipped for, the study of the cellular and molecular basis of occupational and immunologic lung disorders.